This application is entitled to the benefit of and incorporates by reference essential subject matter disclosed in PCT Patent Application No. PCT/JP01/00818 filed on Feb. 6, 2001; Japanese Application No. 2000-288512 filed Sep. 22, 2000; and Japanese Application No. 2000-33459 filed Feb. 10, 2000.
The present invention relates to a granulation coating technique for performing a process such as granulation, coating, mixing, agitation, drying or the like of powder grains with the powder grains fluidized.
A fluidized bed device can perform granulation coating and drying of pharmaceuticals, food or the like within a single device and has an airtight structure, so that it is a suitable device in view of GMP. Therefore, granulation substances obtained by using this have characteristics of comparatively porous and amorphous shapes and good solubility, and so are widely utilized.
While there are many kinds of fluidized bed devices (for example, xe2x80x9cGranulation Handbookxe2x80x9d, edited by The Association of Powder Process Industry and Engineering, Japan, published from Ohmusha, pp. 283-348), the devices are roughly divided into a batch type and a continuous type (including a semi-continuous type and a continuous type) as methods of operation.
Presently, in most cases of performing granulation for pharmaceuticals or the like, the batch type of the device is utilized. This is because the batch type thereof is more suitable for obtaining uniform granulation substances in particle size, and is superior in view of GMP since satisfactory dry products can be obtained within the same device and no generated particles need to be transferred to another drying device.
In contrast thereto, in the continuous type as illustrated, for example, in FIG. 7.56 of page 301 and FIG. 7.57 of page 302 in the xe2x80x9cGranulation Handbookxe2x80x9d, raw materials are continuously injected and granulation substances classified by a principle of gas classification or the like are continuously discharged. This does not need independent steps preceding and following a main step of raw material injection, preliminary mixing, heating, cooling, discharging or the like, and therefore the processing time thereof is shortened. Control and management of the step can be also facilitated since performing stationary operations becomes possible theoretically.
However, particles of all stages of a granulation process are included in a fluidized bed obtained by using the continuous type thereof and are classified by the gas classification and are discharged, so that there are such drawbacks that classification effect is difficult to expect entirely and a particle size distribution of products to be discharged becomes large, and that products to be dried completely are not obtained since the granulation substances are discharged from a fluidizing chamber in which binder liquids are continuously sprayed, and the like.
Suggestions have been made for improving these drawbacks. For example, the device disclosed in Japanese Patent Laid-open No. 62-282629 is provided with a drying chamber adjacent to a granulation chamber, but the drying chamber has a drying effect and contributes to no improvement in a particle size distribution. Also, the devices described in FIG. 7.59 and FIG. 7.61 of page 303 of the xe2x80x9cGranulation Handbookxe2x80x9d are each provided with a classifier to keep particle sizes uniform. However, these devices are each suggested as a system and they themselves are not necessarily improved. Therefore, non-uniformity of particle sizes of the products obtained by the continuous type remains fatefully without being improved.
Also, since the batch type of the device intermittently performs injection and discharge, an operating property of the semi-continuous type has an intermediate property of those of the batch type and the continuous type and the semi-continuous type is a type more similar to either one regarding the relation between an injection and discharge amount and a process amount (a retention amount). Therefore, a merit and demerit of the semi-continuous type has an intermediate property of those of both types.
To compensate for such a demerit of the continuous type as described above, the device of a batch type is used in granulation, coating and the like of pharmaceuticals. However, the device has a problem of scaling up the fluidized bed device as the production thereof is scaled up.
More particularly, upsizing the device causes extensions of the time required for a batch in comparison to a small-sized device, so that the production capacity per unit time does not become proportional to a charge amount but will be below the charge amount. This is because while the amount of charge increases in proportion to a device size to the third power, an amount of fluidizing gas for maintaining an optimal fluidized condition is proportional to the device size to the second power (cross section area) and a drying speed of contents is proportional to the amount of fluidizing gas and so the time required for the drying increases in proportion to the device size.
In a large-sized device, a bulk density of the granulated particles becomes large and thereby the above-mentioned advantages of the fluidized bed granulation substances are reduced. It is thought that this is because the particles continuously repeat movements of dropping to a bottom portion thereof even during fluidization and thereby weight of the particles in being temporally deposited becomes larger than that of a small-sized device.
Even from the viewpoint of operation, the larger the device becomes, the more difficult maintaining a good fluidizing condition becomes and faulty fluidizing conditions such as channeling, bubbling, slagging or the like are likely to occur.
As described above, since it is not favorable to upsize the fluidized bed device to a more degree than a certain degree, small-sized devices with used experience are arranged in parallel and the same granulating processes is performed by at least two of the small-sized devices.
However, in this method, it is likely that there will arise problems of no improvement in a floor area for setting the devices and/or in production efficiency per worker as the production scale is increased, and of being unable to enjoy merits of mass production, and further of non-uniform quality of the granulation substances owing to unevenness of respective operating conditions between the devices. This is because there is also the fact that, in the fluidized beds, the number of operating conditions is large in comparison with other granulating methods and this method is more easily developed than other methods owing to an influence of the unevenness.
The inventors of the present invention have thus come to the idea that it is necessary to develop a device of continuous type, which is capable of improving the production capacity as well as taking advantages of a batch type device.
An object of the present invention is to provide a fluidized bed granulation coating device in which processes that are based on respective steps constituting the fluidized bed granulation coating process are arranged to be of a batch type and such respective processes arranged to be of a batch type are continuously performed.
An object of the present invention is to provide a method of fluidized bed granulation coating, in which batch type operations that are based on respective steps constituting fluidized bed granulation processes are continuously performed.
The fluidized bed granulating coating device of the present invention is characterized by: an intermediate storing section having a plurality of powder grain storing vessels circulated by a circulating means; an upper processing section including a plurality of function stations having respective functions of steps constituting a fluidized bed granulation coating process; and a lower gas supply section having gas supply stations, wherein said powder grain storing vessels of said intermediate storing section is stopped and circulated by said circulating means per each function station, and wherein when said powder grain storing vessels are stopped at said function stations, upper connecting openings of said powder grain storing vessels are connected to lower connecting openings of the respective function stations of said upper processing section and lower connecting openings of said powder grain storing vessels are connected to an upper connecting opening of said gas supply stations of said lower gas supply section.
Said circulating means is, for example, characterized by a rotating means in which said plurality of powder grain storing vessels provided at the same circumferential positions about a rotational center are rotated around said rotational center regarded as a center. Said plurality of function stations is, for example, characterized by including all or a part of a raw material supply station, a granulation coating station, a drying station and a product discharging station.
Said raw material supply station and said product discharging station are, for example, characterized by being constituted by the same station with which a raw material supplying pipe and a product discharging pipe are each provided selectively and usably. Said granulation coating station and said drying station is, for example, characterized by being communicated to a common exhaust opening through a chamber. Said gas supply stations are, for example, characterized by being separated into a fluidized bed forming gas supply stations and a product discharging gas supply station.
Another phase of the present invention is characterized by: using the fluidized bed granulation coating device having any one of the above-mentioned structures; sequentially moving powder grain storing vessels storing powder grains, to function stations having respective functions of steps constituting a fluidized bed granulation coating process in an upper processing section of said fluidized bed granulation coating device, respectively; and supplying gas from a lower gas supply section of said fluidized bed granulation coating device, and thereby performing granulation and/or coating of said power grains accommodated in said powder grain storing vessels.
In a representative fluidized bed granulation coating device of the present invention, to, for example, the function stations having respective functions such as a raw material supplying step, a granulating step, a drying step, a product discharging step and the like constituting the fluidized bed granulating coating process, the plurality of powder grain storing vessels provided at positions radially extending from a rotational center are rotated about the rotational center regarded as a center by a rotating means, and sequentially circulate through the respective function stations. In addition, by gas supply into the powder grain storing vessels from below through the gas supply station, the powder grains accommodated in the powder grain storing vessels can be granulated and coated.
Thus, the fluidized bed granulation coating device of the present invention is constituted so as to take elements of a batch type and elements of a continuous type and have advantages obtained from both types by sequentially circulating, through the function stations, the powder grain storing vessels storing the powder grains.
By utilizing the fluidized bed granulation coating device with such a structure and further using the method of the present invention, in which the powder grains are granulated and coated in a fluidized bed state, while uniformity of particle diameters thereof is ensured, mass productivity achieved through a continuous type can be also ensured.
The present invention further is characterized by: a plurality of powder grain storing vessels moved by a moving means; a plurality of function stations having respective functions of steps constituting a fluidized bed granulation coating process, and disposed in a non-circular state; and gas supply stations provided to correspond to said function stations, wherein said powder grain storing vessels are stopped and moved per each function station by said moving means, and wherein when said powder grain storing vessels are stopped at said function stations, upper connecting openings of said powder grain storing vessels are connected to lower connecting openings of said function stations and lower connecting openings of said powder grain storing vessels are connected to upper connecting openings of said gas supply stations. Said plurality of function stations are characterized by being disposed on a substantially straight line.
Said plurality of function stations are characterized by including all or a part of a raw material supply station, a granulation coating station, a drying station and a product discharging station.
The fluidized bed granulation coating method according to the present invention is characterized by: using the fluidized bed granulation coating device having any one of the above-mentioned structures; and performing granulation and/or coating of said powder grains accommodated in said powder grain storing vessels.